Aluminum n-(3-trifluoromethylphenyl) anthranilate



United States Patent 3,409,655 ALUMINUM N -(3-TRIFLUOROMETHYLPHEN YL) ANTHRANILATE and Yoshiaki Watanabe,

Taisho Pharmaceutical Co., Ltd.,

the formula is disclosed. The material agent.

This invention relates to a novel anthranilic acid derivative. More particularly, this invention relates to aluminum N-(3-trifluoromethylphenyl) anthranilate COO Teruya Seki, Tokyo, Saitama,

Japan, assignors to Tokyo, Japan Filed Feb. 17,

is useful as an anti-inflammatory aluminum N-(3-trifluoromethylphenyl) anthranilate of the present invention, which has no such side effect, being less toxic than the free acid.

The compound of the present invention is prepared as follows:

1 mole of N-(3-trifiuoromethylphenyl) anthranilic acid is added to 1e of sodium hydroxide in 4 and then the precipitated aluminum N-(3-trifiuoromethylphenyl) anthranilate is collected by suction filtration and dried.

The resulting aluminum N-(3-trifluoromethylphenyl) anthranilate is a pale yellow powder, tasteless and odorless.

It is insoluble in water, soluble in methanol, ethanol, acetone, chloroform and benzene and shows an indefinite melting point.

The above mentioned procedure is based on the fact that 4 mole aqueous solution of sodium hydroxide in adding the equivalent of N-(3-trifluoromethylphenyl) anthranilic acid has the pH of 8.3 at to C.

The N-(3-trifiuoromethylphenyl) anthranilic acid used 3,409,655 Patented Nov. 5, 1968 For testing as to toxicity: 100 rug/kg. (milligrams N-(3-trifiuoromethylphenyl) daily to rats orally for one month; this results in a dedeath of 40% of the test rats.

The LD (orally in mice):

The anti-inflammatory activities of N-(3-trifluoromethylphenyl) anthranilic acid and aluminum N-(3-trifluoromethylphenyl) anthranilate:

(1) Measuring the inhibition of edema produced acutely by injection of 1% carrageenin solution into the plantar surface of the hind paw of rats:

N-(3-trifluoromethy1phenyl) anthranilic acid: 50 mg./ kg. orally; effective.

Aluminum N-(S-trifiuoromethylphenyl) anthranilate: 50 mg./kg. orally; effective.

Aluminum N-(3-trifluoromethylphenyl) anthranilate is as effective as N-(3-trifluoromethylphenyl) anthranilic acid.

(2) Measuring the inhibition of ultra-violet injury to guinea pigs. (Wilhelms method):

-(3-trifluoromethylphenyl) anthranilic acid: 15 mg./ kg. orally; 100% inhibited.

Aluminum N-(3-trifluoromethylphenyl) anthranilates: 15 mg./kg. orally; inhibited.

(3) Measuring the inhibition of granuloma formation caused by subcutaneous implantation of cotton pellets into rats. (R. Meiers method):

N-(3-trifluoromethylphenyl) anthranilic acid: daily 30 mg./kg. orally or one week; effective.

Aluminum N-(3-trifluoromethylphenyl) anthranilate: daily 3-0 mg./kg. orally for one week; effective.

The effectiveness of aluminum N-(3-trifluoromethylphenyl) anthranilate is equal to that of N-(B-trifluoromethylphenyl) anthranilic acid.

(4) Measuring the inhibition of granuloma formation caused by intravenous injection of 0.5% croton oil into rats. (H. Selyes method):

N-(3-trifiuoromethylphenyl) anthranilic acid: daily 50 mg./kg. orally for one week; 69.4% inhibited.

Aluminum N-(3-triflnoromethylphenyl) anthranilate: orally for one Week; 71.4% inhibited.

The new compound of the invention is preferably administered orally, for example in the form content of said new compound.

The following example is further illustrative of the invention.

Example phenyl) anthranilic acid is filtered off and the pH of this filtrate adjusted, if necessary, to 8 to 8.5. To the said filtrate, 40 grams (0.5 mole) of aluminum chloride (AlCl -6H O) in 500 milliliters of water is added dropwise with mechanical stirring.

The precipitae is collected by suction filtration, washed with water until the washings become neutral on litmus paper and dried.

The thus-prepared aluminum N-(S-trifluoromethylphenyl) anthranilate amounts to 138.5 grams.

Pale yellow powder.

Al1alySiS.-C42H2'1A1F9N30 I Ca1cd.: C, H, 3.14%; N, 4.84%. Found: C, 58.1%; H, 3.36%; N, 4.68%.

Adjustment of the aforesaid filtrate to pH 8-8.5, if the pH shows more than 8.5, is effected by the addition of requested amounts N-(3-trifluoromethylphenyl) anbecause the said free acid is insoluble the pH does not show less than 8.0

in water.

what is claimed UNITED STATES PATENTS 1,447,501 3/1923 Altwegg 260-448 B 2,640,842. 6/ 1953 Weidenheimer -5 260-439 3,035,091 5/1962 Wygant 260--448 XR 3,144,387 8/1964 Jones.

3,207,779 9/1965 Cutler et al. 260-448 XR TOBIAS E. LEVOW, Primary Examiner. H. M. S. SNEED, Assistant Examiner. 

